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Biomedical subjects

A S Goldsborough

Publications and source records attributed to A S Goldsborough.

6 recordsLinked to original sources
PubMed1996

Reduction of transcription by homologue asynapsis in Drosophila imaginal discs.

The interactions between enhancers and promotor elements that control gene expression are generally considered to act in cis only, but genetic studies suggest that they can also function in trans between non-contiguous DNA molecules. Termed transvection, such trans interactions have been proposed to be responsible for several examples of intragenic complementation in Drosophila. Transvection is thought to depend on the physical proximity of sister chromosomes, because it is inhibited when chromosome rearrangements reduce the pairing of homologues. This led to the suggestion that transvection occurs when enhancer elements on one chromosome regulate expression on the other, with the pairing dependence resulting from a need for proximity between the two copies of the gene. Here we have analysed the levels of transcription from both alleles of the Drosophila Ultrabithorax (Ubx) gene, and report that the predictions of this simple model are not supported. Our findings indicate a more complex level of trans regulation that may have implications for the aetiology of genetic disorders that are influenced by chromosome rearrangements.

Animals↗
PubMed1996

The Drosophila engrailed and invected genes: partners in regulation, expression and function.

We isolated and characterized numerous engrailed and invected alleles. Among the deficiencies we isolated, a mutant lacking invected sequences was viable and phenotypically normal, a mutant lacking engrailed was an embryo lethal and had slight segmentation defects, and a mutant lacking both engrailed and invected was most severely affected. In seven engrailed alleles, mutations caused translation to terminate prematurely in the central or C-terminal portion of the coding sequence, resulting in embryonic lethality and segmentation defects. Both engrailed and invected expression declined prematurely in these mutant embryos. In wild-type embryos, engrailed and invected are juxtaposed and are expressed in essentially identical patterns. A breakpoint mutant that separates the engrailed and invected transcription units parceled different aspects of the expression pattern to engrailed or invected. We also found that both genes cause similar defects when expressed ectopically and that the protein products of both genes act to repress transcription in cultured cells. We propose that the varied phenotypes of the engrailed alleles can be explained by the differential effects these mutants have on the combination of engrailed and invected activities, that engrailed and invected share a regulatory region, and that they encode redundant functions.

Alleles↗
PubMed1995

Tctex2: a sperm tail surface protein mapping to the t-complex.

Transmission ratio distortion (TRD) in mouse t-haplotypes remains the most significant example of meiotic drive in vertebrates. While the underlying mechanism that fuels it is still mysterious, TRD is clearly a complex multigene phenomenon. The characterization of Tctex2 (t-complex testis expressed 2) shows it to be one of several candidates for involvement in TRD. Tctex2 maps to the t-complex and encodes a membrane-associated protein found exclusively on the sperm tail. The t-haplotype form of Tctex2 is aberrant in both the level of its expression and its primary amino acid sequence, but is nonetheless translated and transported to its normal location. The multiple amino acid changes in the t-form make it extremely unlikely that it can function normally and, since it is found on sperm tails, suggest that it may actively interfere with the development of normal gamete function in males. The possible role of Tctex2 in t-complex transmission ratio distortion and sterility is discussed.

Amino Acid Sequence↗
PubMed1994

Allele-specific quantification of Drosophila engrailed and invected transcripts.

Changes in levels of transcription can be difficult to gauge in animals with lethal mutations. For example, mutations in a regulatory region of an essential gene can have secondary consequences that complicate attempts to quantify the transcripts produced by the mutant gene. We describe a method that circumvents this problem by revealing the relative amount of transcript produced from each allele in a heterozygote. With this method, recessive lethal mutations can be analyzed in animals that are phenotypically wild type. We used this technique to analyze mutations in the regulatory region of the Drosophila engrailed gene and found that truncations reduce transcription to levels that depend both upon the tissue and upon the location of the chromosomal break. We also found that these mutations affect expression of the linked invected gene, suggesting that engrailed and invected share a complex set of regulatory elements that operate over at least 85 kb. We suggest that this technique will have general utility for the quantitation of allele-specific transcripts, even when amounts of tissue are limiting.

Alleles↗
PubMed1993

Cloning, chromosomal localization and expression pattern of the POU domain gene Oct-11.

POU domain genes encode a family of highly conserved transacting factors that influence the transcriptional activity of several cell type-specific and ubiquitous genes. We have cloned and sequenced cDNAs encoding a novel mouse POU domain protein, Oct-11, that is closely related within the POU domain to the POU class II proteins, Oct-1 and Oct-2. Recombinant Oct-11 protein binds specifically to an octamer sequence in vitro. The Oct-11 gene is expressed during mouse embryogenesis and in the adult thymus and testis. In addition, it is abundant in the myeloma cell line P3/NS-1/1-Ag4.1. We describe the structure of Oct-11 and its chromosomal localization, and discuss the evidence that the POU class II gene family has evolved by duplication and divergence of a common ancestral gene.

Amino Acid Sequence↗